G-Protein-Coupled Receptor Modulation of Striatal Ca_V1.3 L-Type Ca²⁺Channels Is Dependent on a Shank-Binding Domain

CaV1.3 as pacemaker channels in adrenal chromaffin cells: Specific role on exo- and endocytosis?

“…Spontaneous AP firing, low-threshold exocytosis and compensatory/excess endocytosis are likely to be directly controlled by Ca V 1.3, which then turns out to be an important molecular gateway for controlling catecholamine release and regulate the "fight-or-flight" response under stress condition. Since Ca V 1.3 is also critical for the control of vital functions such as: heart beating, 4 hearing 83 and dopamine release, 5,57 it is evident that the availability of new DHP compounds that selectively block Ca V 1.3 would be beneficial for the therapeutic treatment of Parkinson disease, cardiac arrhythmias, chronic stress and other neuro-and cardiovascular pathologies in which Ca V 1.3 is likely to be involved.…”

Homer proteins in Ca2+ signaling by excitable and non-excitable cells

“…In addition to the mGluRs, many Ca 2+ signaling proteins express Homer ligands and bind Homer. Among them are the scaffolding protein Shank [8], PLCβ [16,17], IP 3 receptors (IP 3 Rs) [15,18], TRPC channels [15,18], ryanodine receptors (RyRs) [19][20][21][22] and selective L-type Ca 2+ channel isoforms [23][24][25].…”

“…However, this effect is likely to be indirect since the Ntype Ca 2+ channels do not posses Homer ligand. The Homers likely recruit the neuronal Ltype Ca 2+ channel Ca v 1.3 to the PSD since disruption of Homer complexes in striatal spiny neurons with an inhibitory peptide disrupted the modulation of Ca v 1.3 by stimulation of the D2 dopaminergic and M1 muscarinic receptors [24], and Ca v 1.3 expresses Homer binding ligand in its C-terminus.…”

“…A role of Homer proteins in E-C coupling is suggested by the presence of a Homer-binding motif in ryanodine receptors (RyRs) and the α1C subunit of Ca v 1.2 and α1D subunit of Ca v 1.3 L type Ca 2+ channels [24,25]. Indeed, measurement of Ca 2+ release in permeabilized skeletal muscle fibers and the activity of RyRs reconstituted into lipid bilayers show that Homer1 activates the skeletal and cardiac muscle RyR isoforms RyR1 [19][20][21] and RyR2 [22].…”

The PDZ Motif of the α1C Subunit Is Not Required for Surface Trafficking and Adrenergic Modulation of CaV1.2 Channel in the Heart

“…Mice with deletion of the Na V 1.5 PDZ motif displayed reduced Na V 1.5 expression and current, specifically at the lateral myocyte membrane, whereas expression and function at the intercalated disks were not altered (51). Ca V 1.3, which is expressed in neurons and in cardiac sinoatrial and atrioventricular nodes and atria, but not in ventricles (57), also contains a C-terminal PDZ ligand motif and binds erbin (58) and shank, both neuronal PDZ domain proteins (23,59).…”